title: Reduced anterior temporal and hippocampal functional connectivity during face processing discriminates individuals with social anxiety disorder from healthy controls and panic disorder, and increases following treatment.
abstract: Group functional magnetic resonance imaging (fMRI) studies suggest that anxiety disorders are associated with anomalous brain activation and functional connectivity (FC). However, brain-based features sensitive enough to discriminate individual subjects with a specific anxiety disorder and that track symptom severity longitudinally, desirable qualities for putative disorder-specific biomarkers, remain to be identified. Blood oxygen level-dependent (BOLD) fMRI during emotional face perceptual tasks and a new, large-scale and condition-dependent FC and machine learning approach were used to identify features (pair-wise correlations) that discriminated patients with social anxiety disorder (SAD, N=16) from controls (N=19). We assessed whether these features discriminated SAD from panic disorder (PD, N=16), and SAD from controls in an independent replication sample that performed a similar task at baseline (N: SAD=15, controls=17) and following 8-weeks paroxetine treatment (N: SAD=12, untreated controls=7). High SAD vs HCs discrimination (area under the ROC curve, AUC, arithmetic mean of sensitivity and specificity) was achieved with two FC features during unattended neutral face perception (AUC=0.88, P<0.05 corrected). These features also discriminated SAD vs PD (AUC=0.82, P=0.0001) and SAD vs HCs in the independent replication sample (FC during unattended angry face perception, AUC=0.71, P=0.01). The most informative FC was left hippocampus-left temporal pole, which was reduced in both SAD samples (replication sample P=0.027), and this FC increased following the treatment (post>pre, t(11)=2.9, P=0.007). In conclusion, SAD is associated with reduced FC between left temporal pole and left hippocampus during face perception, and results suggest promise for emerging FC-based biomarkers for SAD diagnosis and treatment effects.
authors.affiliation: 1] fMRI Research Center, Columbia University Medical Center, New York, NY, USA [2] Department of Physiology and Cellular Biophysics, Columbia University, New York, NY, USA.
authors.forename: Spiro P
authors.initials: SP
authors.lastname: Pantazatos
authors.affiliation: 1] Department of Psychiatry, Columbia University, New York, NY, USA [2] Division of Epidemiology, New York State Psychiatric Institute, New York, NY, USA.
authors.forename: Ardesheer
authors.initials: A
authors.lastname: Talati
authors.affiliation: 1] Department of Psychiatry, Columbia University, New York, NY, USA [2] Anxiety Disorders Clinic, New York State Psychiatric Institute, New York, NY, USA.
authors.forename: Franklin R
authors.initials: FR
authors.lastname: Schneier
authors.affiliation: 1] fMRI Research Center, Columbia University Medical Center, New York, NY, USA [2] Department of Neuroscience, Columbia University, New York, NY, USA [3] Departments of Radiology, Columbia University, New York, NY, USA [4] Department of Psychology, Columbia University, New York, NY, USA.
authors.forename: Joy
authors.initials: J
authors.lastname: Hirsch
mesh_terms: D000293:Adolescent; D000328:Adult; D005149:Facial Expression; D005260:Female; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000503:physiopathology; D016584:Panic Disorder / Q000175:diagnosis / Q000503:physiopathology* / Q000628:therapy; D010698:Phobic Disorders / Q000175:diagnosis / Q000503:physiopathology* / Q000628:therapy; D010775:Photic Stimulation / Q000379:methods; D013702:Temporal Lobe / Q000503:physiopathology*; D016896:Treatment Outcome; D055815:Young Adult